Development of a compartmental model of zinc kinetics in mice.
To investigate zinc (Zn) kinetics in mice, tracer ((65)Zn) was administered orally to 9-wk-old female mice in the fed state and tracer and Zn concentration were measured in 21 tissues over the following 8 d. Data were analyzed by compartmental modeling using WinSAAM. A published model for Zn kinetics in rats was modified to fit the data from mice and to calculate transfer rates and pool sizes of Zn. Parallel studies were performed in mice lacking genes for metallothionein (MT), MT-I and MT-II (MT-/-), to quantify differences in Zn kinetics in the absence of these proteins in vivo. We confirmed that tracer time course in most tissues was similar in wild-type mice and those lacking MT, except for the pancreas of MT-/-, which retained less tracer. By fitting tissue and intestinal data simultaneously, we found that intestinal tracer could be explained by unabsorbed isotope and loss of Zn from pancreas went through plasma. Differences in pancreatic data in MT-/- were explained by Zn turning over twice as fast in this tissue (4 h) compared with wild type (9 h). These kinetic studies provide parameter values for normal, fed mice that can be used to assess Zn kinetics in abnormal conditions, as demonstrated by the higher turnover of Zn in the pancreas of MT knockout mice.
Wastney
Meryl E
ME
Metabolic Modeling Services, 7201 Blenheim, New Zealand. wastneym@metabolic-modeling-services.com
House
William A
WA
D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D017353:Gene Deletion; D008668:Metallothionein / Q000235:genetics / Q000378:metabolism; D051379:Mice; D015032:Zinc / Q000097:blood / Q000493:pharmacokinetics*; D015037:Zinc Radioisotopes / Q000493:pharmacokinetics
D015037:Zinc Radioisotopes; D008668:Metallothionein; D015032:Zinc